ITGB4 Deficiency Induces Mucus Hypersecretion by Upregulating MUC5AC in RSV-infected Airway Epithelial Cells

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2022 Jan 3

PMID 34975337

Citations 6

Authors

Xizi Du

Yu Yang

Ming Yang

Lin Yuan

Leyuan Wang

Mengping Wu

Kai Zhou

Wenkai Li

Yang Xiang

Xiangping Qu

Huijun Liu

Xiaoqun Qin

Chi Liu

Affiliations

Soon will be listed here.

Abstract

Respiratory syncytial virus (RSV) infection is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI), which is closely associated with the occurrence and development of asthma in later life. Integrin β4 (ITGB4) is down-regulated in the airway epithelial cells (AECs) of asthma patients which plays a critical role in the pathogenesis of asthma. However, whether ITGB4 is involved in the pathological processes of RSV infection remains unclear. In this study, we found that decreased expression of ITGB4 was negatively correlated with the level of MUC5AC in childhood AECs following RSV infection. Moreover, ITGB4 deficiency led to mucus hypersecretion and MUC5AC overexpression in the small airway of RSV-infected mice. MUC5AC expression was upregulated by ITGB4 in HBE cells through EGFR, ERK and c-Jun pathways. EGFR inhibitors treatment inhibited mucus hypersecretion and MUC5AC overexpression in ITGB4-deficient mice after RSV infection. Together, these results demonstrated that epithelial ITGB4 deficiency induces mucus hypersecretion by upregulating the expression of MUC5AC through EGFR/ERK/c-Jun pathway, which further associated with RSV-related LRTI.

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